Dipeptidyl peptidase I and III activities of adult schistosomes

Soluble extracts of adult Schistosoma japonicum and S. mansoni were examined for the presence of proteolytic activities ascribable to dipeptidyl peptidases (DPPs) at a range of pH from 4 to 11 using synthetic peptidyl substrates diagnostic of DPPs I, II, III and IV. Activity capable of cleaving the DPP I-specific substrates H-Gly-Arg-NHMec and H-Gly-Phe-NHMec which exhibited a pH optimum of 5.5 was observed in extracts of schistosomes. Female schistosomes exhibited greater DPP I activity than male schistosomes, while female S. japonicum showed substantially more activity than female S. mansoni. The specific activities against H-Gly-Arg-NHMec were 21.5 and 1.9 nmoles NHMec/min/mg protein for female and male S. japonicum and 8.5 and 1.9 nmoles NHMec/min/mg for female and male S. mansoni. The biochemical properties of schistosome DPP I were similar to mammalian DPP I (= cathepsin C) in that schistosome DPP I was only slowly inhibited by the cysteine protease inhibitor trans-epoxysuccinyl-1-leucylamido (4-guanidino)-butane, partly inhibited by the blocked diazomethyl ketones Z-Phe-Ala-CHN₂ and Z-Phe-Phe-CHN₂, but enhanced by halide ions. At pH 8.5, activity against the DPP III-specific substrate H-Arg-Arg-NHMec was evident in schistosome extracts, and this activity appeared to be due to a zinc metallo-exopeptidase because it was inhibited by 1,10-phenathroline and by EDTA. DPP II or DPP IV activity was not detected in the schistosome extracts.